Is FARS2 p.Ala252Pro (c.754G>C) pathogenic?

FARS2 p.Ala252Pro (c.754G>C) is classified Uncertain significance in FARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: ambiguous (0.3516); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FARS2 p.Ala252Pro (c.754G>C)?

FARS2 p.Ala252Pro (c.754G>C) is associated with Inborn genetic diseases (ClinVar).

How common is FARS2 p.Ala252Pro (c.754G>C) in the general population?

FARS2 p.Ala252Pro (c.754G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FARS2 p.Ala252Pro (c.754G>C)?

AlphaMissense predicts ambiguous (score 0.3516) — an in-silico prediction, not a clinical call.

FARS2 p.Ala252Pro

c.754G>C · rs371390356 · VCV2325902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3516 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3516	ambiguous
REVEL	0.081	moderately benign-leaning
SaProt	LLR -10.87	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -3.2, phastCons 0.2
Regional constraint	o/e 0.90	unconstrained · MANE · 403 kb · p 0.021 · regional, not allelic
Overall
CADD	4.38	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FARS2
Protein: p.Ala252Pro
Coding: c.754G>C
MANE Select: NM_006567
dbSNP: rs371390356
Type: single nucleotide variant
Location: chr6:5404683 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.17 · 9 PDB
Residue 252: an α-helix

Full FARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FARS2 p.Ala252Gly Uncertain significance ★★ ⚠ same residue
FARS2 p.Ala252Thr Uncertain significance ★ ⚠ same residue
FARS2 p.Pro361Leu Pathogenic/Likely pathogenic ★★ same condition
FARS2 p.Ala225Val Uncertain significance ★★ ⚠ same condition
FARS2 p.Arg104His Uncertain significance ★★ ⚠ same condition
FARS2 p.Arg338Ser Uncertain significance ★★ same condition
FARS2 p.Arg415Cys Uncertain significance ★★ ⚠ same condition
FARS2 p.Arg423Gln Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fars2-p-ala252pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown